Heparin binding is critical for activities in many cellular growth factors, cell adhesion molecules, and certain enzymes involved in the blood clotting cascade. Agents to inhibit these interactions have found numerous uses in prevention of thrombosis. Heparin analogues have been shown to have anti-tumor and antimetastatic activities.
Peptides that bind to heparin have been identified or isolated from many heparin binding proteins (see, for example Cardin et al, Arteriosclerosis, Vol. 9, pages 21-32 (1989)). Examples of heparin binding peptides identified from adhesion molecules include type IV collagen, laminin, and fibronectin. All have clusters of basic amino acids which fit consensus sequences defined by comparison of many heparin binding proteins (see Cardin et al, as above). The binding constants of the Cardin et al peptides and other peptide described in this art area are in the general range of 10.sup.4 to 10.sup.3 molar.sup.-1.
Peptides from malaria circumsporozoite protein have been disclosed to mediate cell adhesion (Rich et al, Science, Vol 249:1574-1577, (1990)). Such peptides suffer from the disadvantages of not binding heparin and the adhesion activity was ascribed to a sequence Val-Thr-Cys-Gly, which is inactive for heparin binding.
Peptides from thrombospondin have been disclosed (Prater et al, J. Cell Biol. Vol 112, pages 1031-1040 (1992)). The sequences of Prater have a significant disadvantage since they are insufficient to bind to heparin or related sulfated glycoconjugates with high affinity.
Accordingly, there is a need in the present art for highly potent peptides that will bind to heparin or related sulfated glycoconjugates with high affinity. There is particularly a need for such peptides which are also useful to prevent interaction of heparin or related sulfated glyconjugates with adhesion molecules, growth factors, cells or heparin-dependent enzymes.